This research proposal is aimed at investigating mechanisms that predispose to chronic pulmonary disease. Studies of alpha-l-antitrypsin deficiency will be continued in order to perfect simplified methods for its detection that would allow generalized availability to clinical laboratories. Mechanisms involved in the development of antitrypsin deficiency will also be studied. The usefulness of measuring serum angiotensin-converting-enzyme (ACE) for confirming a diagnosis of sarcoidosis will continue to be evaluated. The role of the enzyme elevation in the pathogenesis of this disease will also be investigated, and the possibility that hyper-activated macrophages are the source of this enzyme elevation will be considered. Other diseases that may have associated elevation of serum ACE will be sought. Abnormalities in lymphocyte transformation in cystic fibrosis will continue to be studied. Usefulness of this phenomenon for detecting the heterozygous (carrier) state, and the role of a serum factor for affecting lymphocyte transformation in cystic fibrosis will be studied. Other mechanisms being studied include possible genetic variation in leukocyte protease content as a predisposing factor for emphysema, and aryl-hydrocarbon-hydroxylase for lung cancer.